title: Effects of deltamethrin on excitability and contractility of the rainbow trout (Oncorhynchus mykiss) heart.
abstract: Pyrethroids are extensively used for the control of pest insects and disease vectors. Pyrethroid use is regarded safe due to their selective toxicity: they are effective against insects but relatively harmless to mammals and birds. Unfortunately, pyrethroids are very toxic to fishes. The high toxicity of pyrethroids to fishes is only partly explained by slow elimination rate of toxins, suggesting that high affinity binding to their molecular targets, the Na(+) channels, is involved. This study tests the hypothesis that Na(+) channels of the fish heart are targets to a type II pyrethroid, deltamethrin (DM), and therefore pyrethroids are cardiotoxic to fishes. In ventricular myocytes of the rainbow trout (Oncorhynchus mykiss) heart DM (10(-7)-3·10(-5) M) modified Na(+) current by slowing inactivation and shifting the reversal potential of the current to the left. Maximally 31±2% of the cardiac Na(+) channels were modified by DM and the half-maximal effect occurred at the concentration of 2.1 μM. The effect of DM on trout cardiac Na(+) channels is stronger and occurs about an order of magnitude lower in concentration in comparison to the orthologous mammalian Na(+) channels. In sinoatrial preparations of the trout heart DM (10 μM) caused irregularities in rate, rhythm and force of the heartbeat indicating that DM can be arrhythmogenic for the trout heart. Consistent with this, DM (>0.1 μM) induced spontaneous action potentials in otherwise quiescent ventricular myocytes. DM (10 μM) did not affect calcium current or inward rectifier and delayed rectifier potassium currents. Collectively, these findings indicate that DM exerts cardiotoxic effects in trout, and suggest that the high sensitivity of fishes to pyrethroid toxicity might be partially due to the high affinity of fish Na(+) channels to pyrethroids.
authors.affiliation: University of Eastern Finland, Department of Biology, P.O. Box 111, 80101 Joensuu, Finland. Electronic address: jaakko.haverinen@uef.fi.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Haverinen
authors.forename: Matti
authors.initials: M
authors.lastname: Vornanen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology*; D017686:Oncorhynchus mykiss / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D011722:Pyrethrins / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; C017180:decamethrin; D011188:Potassium; D002118:Calcium
keywords: Cardiac arrhythmias; Deltamethrin; Excitation–contraction coupling; Heart; Pyrethroids; Rainbow trout; Sodium current